Distribution profile and properties of peripheral-type benzodiazepine receptors on human hemopoietic cells

Canat, Xavier; Carayon, Pierre; Bouaboula, Monsif; Cahard, Dominique; Shire, David; Roque, Claude; Fur, G. Le; Casellas, Pierre

doi:10.1016/0024-3205(93)90293-c

Cited by 133 publications

(104 citation statements)

References 34 publications

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“…44,45 Animal studies have shown that the TSPO signal in brain is mainly derived from microglia, 20,46 with a significant contribution from astrocytes during certain conditions. 19,47 Apart from these resident immune cell populations, peripherally derived myeloid cells in the form of infiltrating or perivascular macrophages may also contribute to the signal.…”

Section: Forsberg Et Al: Brain After Abdominal Surgerymentioning

confidence: 99%

The immune response of the human brain to abdominal surgery

Forsberg

Červenka

Fagerlund

et al. 2017

Annals of Neurology

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Objective: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short-and longterm impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. Methods: Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [ 11 C]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed. Results: Patients showed a global downregulation of gray matter [ 11 C]PBR28 binding of 26 6 26% (mean 6 standard deviation) at 3 to 4 days postoperatively compared to baseline (p 5 0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-a in blood displayed a reduction (41 6 39%) on the 3rd to 4th postoperative day, corresponding to changes in [ 11 C]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [ 11 C]PBR28 binding (p 5 0.027). Interpretation: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function. ANN NEUROL 2017;81:572-582 A growing body of evidence suggests that surgical trauma launches a systemic inflammatory response that ultimately reaches and activates the intrinsic immune system of the brain. [1][2][3][4] Triggered by surgery-induced damage-associated molecular patterns (DAMPs), an array of proinflammatory mediators and activated blood-borne immune cells orchestrate a rapid spread of this systemic response to the central nervous system (CNS), with inflammatory markers detectable in human cerebrospinal fluid (CSF) within 12 hours. [4][5][6][7] In surgical rodent models, this periphery-to-brain pathway seems critically dependent on NF-jB and proinflammatory cytokine signaling (eg, tumor necrosis factor-a [TNF-a]) associated with a shortlasting disruption of blood-brain barrier integrity, 2,3,8 migration of peripheral macrophages into the CNS, and subsequent hippocampal neuronal dysfunction and cognitive impairment. 8 In addition to an acute and transient response, often referred to as a syndrome of sickness behavior including fatigue, anorexia, and fever, surgery-induced immune activation may be associated with prolonged impairments in learning,...

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Section: Forsberg Et Al: Brain After Abdominal Surgerymentioning

confidence: 99%

The immune response of the human brain to abdominal surgery

Forsberg

Červenka

Fagerlund

et al. 2017

Annals of Neurology

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“…Leukocyte cell subpopulations were purified as previously described (Canat et al, 1993). Human blood was obtained from healthy volunteer donors.…”

Section: Preparation Of Human Leucocyte Cell Subpopulationsmentioning

confidence: 99%

Cannabinoid‐receptor expression in human leukocytes

Bouaboula

Rinaldi

Carayon

et al. 1993

European Journal of Biochemistry

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Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS), probably through the cannabinoid receptor, which has recently been cloned in rat and human. While numerous reports have also described effects of cannabinoids on the immune system, the observation of both mRNA and cannabinoid receptor has hitherto been exclusively confined to the brain, a reported detection in the testis being the sole example of its presence at the periphery. Here we report the expression of the cannabinoid receptor on human immune tissues using a highly sensitive polymerase-chain-reaction-based method for mRNA quantification. We show that, although present in a much lower abundance than in brain, cannabinoid receptor transcripts are found in human spleen, tonsils and peripheral blood leukocytes. The distribution pattern displays important variations of the mRNA level for the cannabinoid receptor among the main human blood cell subpopulations. The rank order of mRNA levels in these cells is B cells > natural killer cells 2 polymorphonuclear neutrophils 2 T8 cells > monocytes > T4 cells. Cannabinoid-receptor mRNA, which is also found in monocytic, as well as T and B leukemia cell lines but not in Jurkat cells, presents a great diversity of expression on these cells as well, B-cell lines expressing a much higher level than T-cell lines. The cannabinoid receptor PCR products from leukocytes and brain are identical both in size and sequence suggesting a strong similarity between central and peripheral cannabinoid receptors. The expression of this receptor was demonstrated on membranes of the myelomonocytic U937 cells using the synthetic cannabinoid [3H]CP-55940 as ligand. The Kd determined from Scatchard analysis was 0.1 nM and the B,, for membranes was 525 fmol/mg protein. The demonstration of cannabinoid-receptor expression at both mRNA and protein levels on human leukocytes provides a molecular basis for cannabinoid action on these cells.

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“…11 C-(R)-PK11195 specifically targets the 18-kd translocator protein, which was previously known as peripheral benzodiazepine receptor, a mitochondrial membrane protein that is up-regulated in activated macrophages (10). Macrophages infiltrate synovial tissue during the early development of RA (11).…”

mentioning

confidence: 99%